The Discovery and Characterization of a Potent DPP-IV Inhibitory Peptide from Oysters for the Treatment of Type 2 Diabetes Based on Computational and Experimental Studies
Zhongqin Chen,
Xiaojie Su,
Wenhong Cao,
Mingtang Tan,
Guoping Zhu,
Jialong Gao,
Longjian Zhou
Affiliations
Zhongqin Chen
Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China
Xiaojie Su
Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China
Wenhong Cao
Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China
Mingtang Tan
Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China
Guoping Zhu
Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Provincial Engineering Technology Research Center of Prefabricated Seafood Processing and Quality Control, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
Jialong Gao
Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Provincial Engineering Technology Research Center of Prefabricated Seafood Processing and Quality Control, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
Longjian Zhou
Shenzhen Institute of Guangdong Ocean University, Shenzhen 518120, China
The inhibition of dipeptidyl peptidase-IV (DPP-IV) is a promising approach for regulating the blood glucose levels in patients with type 2 diabetes (T2D). Oysters, rich in functional peptides, contain peptides capable of inhibiting DPP-IV activity. This study aims to identify the hypoglycemic peptides from oysters and investigate their potential anti-T2D targets and mechanisms. This research utilized virtual screening for the peptide selection, followed by in vitro DPP-IV activity assays to validate the chosen peptide. Network pharmacology was employed to identify the potential targets, GO terms, and KEGG pathways. Molecular docking and molecular dynamics simulations were used to provide virtual confirmation. The virtual screening identified LRGFGNPPT as the most promising peptide among the screened oyster peptides. The in vitro studies confirmed its inhibitory effect on DPP-IV activity. Network pharmacology revealed that LRGFGNPPT exerts an anti-T2D effect through multiple targets and signaling pathways. The key hub targets are AKT1, ACE, and REN. Additionally, the molecular docking results showed that LRGFGNPPT exhibited a strong binding affinity with targets like AKT1, ACE, and REN, which was further confirmed by the molecular dynamics simulations showcasing a stable peptide–target interaction. This study highlights the potential of LRGFGNPPT as a natural anti-T2D peptide, providing valuable insights for potential future pharmaceutical or dietary interventions in T2D management.
